L2: Red cell, Hb and Anaemia

Question 1

RBC shape

Answer 1

• Discoid, 7um diameter, no nucleus or RNA
  Shape:
• Increased area for gas exchange
• Allows deformity through capillaries
• Determined by membrane and cytoskeleton proteins
• Abnormalities membrane = shortened lifespan of red cells e.g. hereditary spherocytosis

Question 2

RBC - no mitochondria or RNA

Answer 2

= Keeps Hb in reduced state and maintains osmotic equilibrium

• Glycolysis produces ATP which maintains osmotic equilibrium
• HMP shunt produces NADPH which keeps Hb reduced
• Clinical implication: inherited defects in enzyme pathways leads to haemolysis e.g. GDPD enzyme deficiency

Question 3

RBC - Hb

Answer 3

• In adults HbA is the principle Hb (2 alpha globin chains, 2 beta globin chains and haem group)
• Deficiency of iron –> reduced production of haem –> low Hb (anaemia)
• Impaired production of globin chains –> low Hb –> thalassemia

Question 4

RBC origin

Answer 4

• Arise from myeloid multlineage progenitor in response to GFs: IL-3 and GM-CSF
  (stem cells –> committed progenitor –> RBC)

Question 5

RBC development

Answer 5

Changes with differentiation:

• Progressive increase in Hb
• Chromatin clumping
• Extrude nucleus
• Loss of RNA

Kinetics of erythropoiesis:

• 4 cell cycles/divisions
• 1 pronormoblast –> 16 RBCs
• Process 7-10 days
• Reticulocyte 2 days (last stage before mature)

Question 6

Regulation of erythropoiesis

Answer 6

Erythropoietin:

• Glycoprotein
• Produced in kidney
• Responds to low oxygen tensions (sensed by cells in kidney) by increased erythropoietin production

Question 7

Effects of erythropoietin

Answer 7

Binds to erythropoietin receptor to increase red cell production:
- Stimulation of BFU-E and CFU-E
- Increased Hb synthesis
- Reduced RBC maturation time
- Increased reticulocyte release
= increased Hb therefore increased oxygen delivery

Question 8

Clinical implications of erythropoietin

Answer 8

• Clinical use of recombinant EPO: anaemia of renal failure and other anaemias e.g. myelodysplastic syndromes
• Potential for abuse e.g. endurance sports
• Can lead to thromobotic events (due to high Hb)

Question 9

RBC destruction

Answer 9

• Average lifespan 120 days
• Cells become less deformable and are removed in liver and spleen
• Breakdown of RBCs with release of Hb
• Hb broken down into: globin chains and haem
  –> iron back into BM
  –> protoporphyrin into bilirubin liver into
  bile (haemolysis = jaundice due to uncongugated bilirubin)

Question 10

Anaemia general

Answer 10

• Hb lower than normal for age and sex
• Hb higher at birth then falls from 3months-1yr then increases with age
• Hb higher in males than females

Question 11

Body’s response to anaemia

Answer 11

Increased cardiac output:

• Increased SV
• Increased HR
• A right shift in Hb dissociation curve
• Rise in 2,3 DPG levels

i.e. makes oxygen more readily available to tissues

Question 12

Classification of anaemia

Answer 12

Physiologic: impaired production vs blood loss/reduced survival of cells (haemolysis)
OR
Morphology: size of cells microcytic or macrocytic